The main objectives of this application are: (1) to determine, in general, the role of membrane acidic lipids in drug-receptor interaction, with special emphasis on establishing the role of cerebroside sulfate (CS) in opiate receptor mechanism as well as its role in the pharmacologic actions of opiates and opioid peptides in vivo; (2) to understand the molecular mechanism of opiate agonist-receptor and antagonist-receptor interactions, using CS as a model opiate receptor; (3) to determine the chemical nature of opiate receptors in synaptic plasma membrane (SPM) and in neuroblastoma glioma hybrid cells by chemicals which label the receptor irreversibly; (4) to use neuroblastoma, glioma and hybrid cells to further establish the role of membrane lipids in opiate receptor mechanism and explore the possibility of using this cell culture and cell fusion technique to study opiate receptor binding and receptor function correlates. The rationale for these proposals was derived from the following theoretical and experimental observations: (a) Lipids are predominant and essential components of cell membranes and as such, play important structural and functional roles within membranes; (b) Opiate receptors are located in nerve membranes and morphine profoundly affects lipid metabolism in nerve cells; (c) CS is a component of brain tissue and has been found to be a receptor component by labelling with I125-diazosulfonilic acid. A partially purified opiate receptor from mouse brain (Lowney et al) has been shown to be CS: (d) The binding of opiates to CS in vitro is stereospecifically saturable and with high affinity; (e) In vivo experiments indicate that reduced availability of brain CS parallels both the reduction in number of opiate binding sites and the analgetic effects of morphine; (f) Since isolation and purification of opiate receptor has not been achieved and our evidence indicates that CS fulfills most criteria for identifying opiate receptor, it is both important to further establish a role of CS in opiate receptor mechanism and to use CS as a model opiate receptor to study the molecular mechanism of opiate-receptor interactions.